Competition (‘Steal’ Phenomenon) between [68Ga]Ga-PSMA-11 Uptake in Prostate Tumor Tissue Versus Healthy Tissue

Sar, Esmée C. A. van der; Keizer, Bart de; Lam, Marnix G. E. H.; Braat, Arthur J. A. T.

doi:10.3390/pharmaceutics13050699

Cited by 2 publications

(3 citation statements)

References 37 publications

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“…In the current study, however, the number of treatment cycles has a direct relationship with the occurrence of significant bone marrow toxicity, which suggests that while dose-de-escalation may be effective in mitigating the impact of treatment on salivary gland function, administering more cycles of treatment exposes the patients to a higher risk of significant hematologic toxicity. Some recent studies have shown the dynamics of radioligand uptake in normal organs as a function of tumor burden [37,38,39]. These studies, mostly validating the concept of the "tumor sink effect," support our dose-de-escalation practice.…”

Section: Discussionmentioning

confidence: 65%

Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer

Lawal

Morgenstern

Vorster

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose: Actinium-225-labeled prostate-specific membrane antigen ([ 225 Ac]Ac-PSMA-617) is safe and effective in the treatment of metastatic castration-resistant prostate cancer (mCRPC). No study has specifically assessed its safety in patients with extensive skeletal metastases of mCRPC. We aimed to investigate the hematologic toxicity and efficacy of [ 225 Ac]Ac-PSMA-617 therapy in patients with extensive skeletal metastases of mCRPC. Methods:We retrospectively reviewed the medical record of patients treated with [ 225 Ac]Ac-PSMA-617 for mCRPC. We included patients with a superscan pattern of skeletal metastases and those with 20 or more multifocal sites of skeletal metastases on baseline [ 68 Ga]Ga-PSMA-11 PET/CT. We reviewed the levels of hemoglobin, white blood cell (WBC), and platelet prior to each cycle of treatment and determined the presence of impaired bone marrow function at baseline and the grade of toxicity in the hematologic parameters induced by treatment. We evaluated the predictors of hematologic toxicity using binary logistic regression analysis. We also determined the presence of renal dysfunction before or during treatment. We assessed response to treatment using prostate-specific antigen response and the progression-free survival (PFS) and overall survival (OS).Results: A total of 106 patients were included. Skeletal metastasis was in the superscan pattern in 34 patients (32.1%) and multifocal in 72 patients (67.9%). The median treatment cycle was 4 (range = 1-9). Ninety-eight patients (92.5%) had abnormal baseline hematologic parameters. One patient had grade 4 thrombocytopenia. Grade 3 anemia, leukopenia, and thrombocytopenia were seen in 1 (0.9%), 3 (2.8%), and 2 (1.9%) patients, respectively. Age, the number of treatment cycles, and the presence of renal dysfunction were significant predictors of hematologic toxicity. Eighty-five patients (80.2%) achieved PSA response. The median PFS and OS of the study population were 14:00 (95%CI: 8.15-19.86) months and 15.0 (95%CI: 12.8-17.2) months, respectively.Conclusions: [ 225 Ac]Ac-PSMA-617 induces a good anti-tumor effect in about 80% of patients with extensive skeletal metastases of mCRPC with a rare incidence of severe hematologic toxicity. Age, number of treatment cycles, and the presence of renal dysfunction were significant risk factors for hematologic toxicity of [ 225 Ac]Ac-PSMA-617 therapy.

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Section: Discussionmentioning

confidence: 65%

Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer

Lawal

Morgenstern

Vorster

et al. 2022

Eur J Nucl Med Mol Imaging

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“…Fourth, PERCIST for the lesion-based response evaluation is not validated for PSMA PET/CT. However, it is already broadly available in clinical practice and easy to apply [ 15 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…The PET reconstruction was obtained following the EANM Research Ltd. (EARL), Vienna, Austria recommendations although its use for [ 68 Ga]Ga-PSMA-11 PET/CT interpretation has not been validated yet [ 14 , 15 ]. The [ 68 Ga]Ga-PSMA-11 accumulation was corrected for lean body mass (in SUV lbm,peak *cm 3 ) [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Baseline Imaging Derived Predictive Factors of Response Following [177Lu]Lu-PSMA-617 Therapy in Salvage Metastatic Castration-Resistant Prostate Cancer: A Lesion- and Patient-Based Analysis

et al. 2022

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Earlier studies have mostly identified pre-therapeutic clinical and laboratory parameters for the prediction of treatment response to [177Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [68Ga]Ga-PSMA-11 PET/CT can potentially predict the response after two cycles of [177Lu]Lu-PSMA-617 treatment, in a lesion- and patient-based analysis in men with mCRPC. Included patients had histologically proven mCRPC and a [68Ga]Ga-PSMA-11 PET/CT before and after two cycles of [177Lu]Lu-PSMA-617 treatment. The imaging-based response was evaluated on lesion-level (standardized uptake value (SUV) reduction) and patient-level (total lesion PSMA (TL-PSMA) reduction). In the lesion-level analysis, a clear relationship was found between SUVpeak/max and the imaging-based response to [68Ga]Ga-PSMA-11 PET/CT (most avid lesion SUVpeak/max ≥30% reduction) (p < 0.001), with no significant difference in cut-off values between different sites of metastases (i.e., lymph node, bone or visceral metastasis). In patient-level analysis, baseline PSA and SUVpeak values of most avid metastasis were significantly associated with imaging-based response (TL-PSMA ≥30% reduction) (p = 0.019 and p = 0.015). In pre-treatment with [68Ga]Ga-PSMA-11 PET/CT, a clear accumulation-response relationship in lesion-level was found for SUVpeak/max in men with mCRPC receiving two cycles of [177Lu]Lu-PSMA-617 treatment. The SUVpeak of the most avid lesion was the only image-derived factor predictive of the imaging-based response at the patient-level.

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Competition (‘Steal’ Phenomenon) between [68Ga]Ga-PSMA-11 Uptake in Prostate Tumor Tissue Versus Healthy Tissue

Cited by 2 publications

References 37 publications

Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer

Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer

Baseline Imaging Derived Predictive Factors of Response Following [177Lu]Lu-PSMA-617 Therapy in Salvage Metastatic Castration-Resistant Prostate Cancer: A Lesion- and Patient-Based Analysis

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